JOHN F. ASH
Professor of Neurobiology and Anatomy
Molecular physiology of membrane transport
The multiple roles of membrane transport are the subject of Dr. Ash's work. His laboratory currently studies two distinct transport systems: amino acid transporters in cultured mammalian cells and the sodium pump in planaria. The studies of glutamate uptake by cultured cells employ a combination of genetic, molecular, physiological, and structural approaches. Recent results demonstrate that glutamate transport indirectly energizes the uptake of cystine, most likely by exchange reactions. Cystine is required for the synthesis of glutathione, a vital intracellular antioxidant that protects cells, such as metabolically active neurons, from lethal oxidative damage. A new project focuses on understanding the activity and regulation of the sodium pump in planaria. Study of this vital enzyme has largely been limited to higher animals and a companion analysis in a primitive invertebrate will provide a useful perspective. Biochemical and genetic sequence studies demonstrate that planaria have two enzyme isoforms. We are preparing to determine the tissue distribution of these forms and the potential for their differential control by endogenous inhibitory hormones.
Igo, R.P., and Ash, J.F. (1998) The Na+-dependent glutamate and aspartate transporter supports glutathione maintenance and survival of CHO-K1 cells. Somat. Cell Mol. Genet., 24:341-352.
Levy, L.M., Attwell, D., Hoover, F., Ash, J.F., Bjoras, M., and Danbolt, N.C. (1998) Inducible expression of the GLT-1 glutamate transporter in a CHO cell line selected for low endogenous glutamate uptake. FEBS Lett., 422:339-342.
Tong, X., Ash, J.F., and Caldwell, K.D. (1997) Rapid swelling of a CHO-K1 aspartate/glutamate transport mutant in hypo-osmotic medium. J. Membrane Biol, 156:131-139.
Igo, R.P., and Ash, J.F. (1996) New mutations and phenotypes associated with glutamate and aspartate transport in Chinese hamster ovary (CHO-K1) cells. Somat. Cell Mol. Genet., 22:87-103.
Igo, R.P., and Ash, J.F. (1995) Novel regulations of glutamate and aspartate uptake by HeLa. Biochim. et Biophys. Acta., 1233:153-162.